Professor of Anesthesiology, Perioperative and Pain Medicine (Pediatric Anesthesia) at the Stanford University Medical Center and of Pediatrics at the Lucile Salter Packard Children's Hospital

Bio

Bio

Elliot Krane was born in Philadelphia, PA but from the age of 3 months grew up in Tucson, Arizona, the son of a watchmaker and a bookkeeper. He attended Reed College in Portland, Oregon where he had the Dana Scholarship for Excellence in Humanities and graduated Phi Beta Kappa, then returned to Tucson to attend medical school at the University of Arizona. He took a 13 month leave of absence during medical school to work in the Physiological Laboratory at Cambridge University under the mentorship of Peter Nathanielsz, MD, PhD, introducing the laboratory to computerized data recovery and Fourier analysis of EEG for fetal EEG measurement. After being inducted into Alpha Omega Alpha and graduation from the UA, he trained in pediatrics at the Massachusetts General Hospital, then in anesthesiology, also at the MGH, followed by a fellowship year in pediatric anesthesiology and critical care at Boston Children's Hospital.

After this medical training he moved to Seattle, WA to start an academic career at the University of Washington and the Seattle Children's Hospital (then called Children's Orthopedic Hospital). There he and his colleague Donald C. Tyler, MD started the first (or maybe it was the second) pain clinic for children in the U.S.

In 1994 he left the Northwest to continue his career as the Chief of Pediatric Anesthesiology and Professor at Stanford University. He remained the Anesthesiology Chief for the Packard Children's Hospital until 2003, at which time he stepped down to continue as the Chief of Pain Management, the position he holds today. He holds board certification in Pediatrics, Anesthesiology, Pediatric Anesthesiology, Critical Care Medicine, and Pain Management, and is a Fellow of the American Academy of Pediatrics.

Elliot Krane has received the Physician’s Recognition Award in both Anesthesiology and Pediatric Critical from the American Medical Association, the Poster Award from the Vienna International Congress on Anesthesiology and Perioperative Care, the Jeffrey Lawson Award for Advocacy in Children’s Pain Relief from the American Pain Society, and the Ellis N. Cohen Achievement Award from the Stanford University Department of Anesthesiology, Perioperative and Pain Medicine. He has also been the recipient of grants from the Mayday Fund, the NIH, the American Medical Association, the Washington State Society of Anesthesiologists, the Diabetes Research and Education Foundation, and the American Society of Anesthesiologists as well as many pharmaceutical companies to assist them in new drug development for the treatment of pediatric pain.

Elliot now lives in Menlo Park with his wife Maria Amundson, a Stanford Distinguished Careers Fellow, her daughter, and two Australian terriers. His adult sons live in the Bay Area, and his adult step-son studies at, and plays varsity baseball for UCSD.

The purpose will be to study the functional impact of pediatric chronic pain on children, and
their families. Focus will be on the impact of pain on school functioning, social
functioning, psychological functioning and family functioning of pediatric chronic pain.

Efficacy and Safety of ALGRX 3268 in Children Undergoing Minor Needle-Stick Procedures.Not Recruiting

Minor needlestick procedures often cause significant pain and distress in pediatric patients
yet interventions to reduce pain are used infrequently. ALGRX 3268 is a novel, single-use,
prefilled, needle-free product that immediately delivers powdered lidocaine into the
epidermis and provides local analgesia in 2-3 minutes. The purpose of this phase III,
prospective, randomized, double-blind, placebo-controlled study is to investigate the
efficacy, safety and tolerability of ALGRX 3268 versus placebo in pediatric patients aged 3
to 18 years undergoing venipuncture or peripheral venous canulation procedures. The trial
will enroll approximate 504 evaluable subjects at centers located in the US.

To implement a new method of performing chest CT imaging in young children at Packard
Children's Hospital entitled controlled ventilation infant/young child chest CT scanning.
This technique will be used to evaluate early lung disease comparing quantitative chest CT
air trapping and airway measurements with lung function measurements in infants, toddlers,
and young children with chronic lung disease.

Stanford is currently not accepting patients for this trial.For more information, please contact Yan Ki Angela Leung, 650-723-5193.

Measuring the Amount of Methadone or Morphine in the Blood of Neonates, Infants & Children After Cardiac Surgery.Not Recruiting

Study Population:
Neonates, infants and children from birth to 5 years of age undergoing cardiac surgery with
CPB.
The use of methadone to provide analgesia may be increasing due to advantages compared to
other commonly used opioid analgesic drugs. While efficacy of methadone has been reported in
adults, there is a paucity of information in neonates and infants. In the latter population,
fentanyl and morphine are most commonly used for opioid analgesia following major surgery,
while methadone is frequently used for weaning of opioid dependent and tolerant patients, in
spite of the paucity of knowledge of methadone pharmacology in this population. There are
several clinical problems associated with fentanyl and morphine, and methadone may offer
superior efficacy with fewer side effects than these agents. We propose to study the
pharmacokinetics (PK) and pharmacodynamics (PD) of methadone in neonates and infants in the
intensive care unit following cardiac surgery.

Stanford is currently not accepting patients for this trial.For more information, please contact Gregory Hammer, (650) 723 - 7835.

Abstract

The pediatric adaptation of the Collaborative Health Outcomes Information Registry (Peds-CHOIR) is a free, open-source, flexible learning health care system (LHS) that meets the call by the Institute of Medicine for the development of national registries to guide research and precision pain medicine. This report is a technical account of the first application of Peds-CHOIR with 3 aims: (1) to describe the design and implementation process of the LHS; (2) to highlight how the clinical system concurrently cultivates a research platform rich in breadth (eg, clinic characteristics) and depth (eg, unique patient- and caregiver-reporting patterns); and (3) to demonstrate the utility of capturing patient-caregiver dyad data in real time, with dynamic outcomes tracking that informs clinical decisions and delivery of treatments. Technical, financial, and systems-based considerations of Peds-CHOIR are discussed. Cross-sectional retrospective data from patients with chronic pain (N = 352; range, 8-17 years; mean, 13.9 years) and their caregivers are reported, including National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) domains (mobility, pain interference, fatigue, peer relations, anxiety, and depression) and the Pain Catastrophizing Scale. Consistent with the literature, analyses of initial visits revealed impairments across physical, psychological, and social domains. Patients and caregivers evidenced agreement in observable variables (mobility); however, caregivers consistently endorsed greater impairment regarding internal experiences (pain interference, fatigue, peer relations, anxiety, and depression) than patients' self-report. A platform like Peds-CHOIR highlights predictors of chronic pain outcomes on a group level and facilitates individually tailored treatment(s). Challenges of implementation and future directions are discussed.

Abstract

An ideal taxonomy of chronic pain would be applicable to people of all ages. Developmental sciences focus on lifespan developmental approaches, and view the trajectory of processes in the life course from birth to death. In this article we provide a review of lifespan developmental models, describe normal developmental processes that affect pain processing, and identify deviations from those processes that lead to stable individual differences of clinical interest, specifically the development of chronic pain syndromes. The goals of this review were 1) to unify what are currently separate purviews of "pediatric pain," "adult pain," and "geriatric pain," and 2) to generate models so that specific elements of the chronic pain taxonomy might include important developmental considerations.A lifespan developmental model is applied to the forthcoming Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy to ascertain the degree to which general "adult" descriptions apply to pediatric and geriatric populations, or if age- or development-related considerations need to be invoked.

Abstract

The impact of the patient state at time of placement of regional blocks on the risk of complications is unknown. Current opinion is based almost entirely on case reports, despite considerable interest in the question. Analyzing more than 50,000 pediatric regional anesthesia blocks from an observational prospective database, we determined the rate of adverse events in relation to the patient's state at the time of block placement. Primary outcomes considered were postoperative neurologic symptoms (PONSs) and local anesthetic systemic toxicity (LAST). Secondary outcome was extended hospital stay due to a block complication.The Pediatric Regional Anesthesia Network is a multi-institutional research consortium that was created with an emphasis on rigorous, prospective, and complete data collection including a data validation and audit process. For the purpose of the analysis, blocks were divided in major groups by single injection versus continuous and by block location. Rates were determined in aggregate for these groups and classified further based on the patient's state (general anesthesia [GA] without neuromuscular blockade [NMB], GA with NMB, sedated, and awake) at the time of block placement.Postoperative neurological symptoms occurred at a rate of 0.93/1000 (confidence interval [CI], 0.7-1.2) under GA and 6.82/1000 (CI, 4.2-10.5) in sedated and awake patients. The only occurrence of PONSs lasting longer than 6 months (PONSs-L) was a small sensory deficit in a sedated patient (0.019/1000 [CI, 0-0.1] for all, 0.48/1000 [CI, 0.1-2.7] for sedated patients). There were no cases of paralysis. There were 5 cases of LAST or 0.09/1000 (CI, 0.03-0.21). The incidence of LAST in patients under GA (both with and without NMB) was 0.08/1000 (CI, 0.02-0.2) and 0.34/1000 (CI, 0-1.9) in awake/sedated patients. Extended hospital stays were described 18 times (0.33/1000 [CI, 0.2-0.53]). The rate for patients under GA without NMB was 0.29/1000 (CI, 0.13-0.48); GA with NMB, 0.29/1000 (CI, 0.06-0.84); sedated, 1.47/1000 (CI, 0.3-4.3); and awake, 1.15/1000 (CI, 0.02-6.4).The placement of regional anesthetic blocks in pediatric patients under GA is as safe as placement in sedated and awake children. Our results provide the first prospective evidence for the pediatric anesthesia community that the practice of placing blocks in anesthetized patients should be considered safe and should remain the prevailing standard of care. Prohibitive recommendations based on anecdote and case reports cannot be supported.

Abstract

Regional anesthesia is increasingly used in pediatric patients to provide postoperative analgesia and to supplement intraoperative anesthesia. The Pediatric Regional Anesthesia Network was formed to obtain highly audited data on practice patterns and complications and to facilitate collaborative research in regional anesthetic techniques in infants and children.We constructed a centralized database to collect detailed prospective data on all regional anesthetics performed by anesthesiologists at the participating centers. Data were uploaded via a secure Internet connection to a central server. Data were rigorously audited for accuracy and errors were corrected. All anesthetic records were scrutinized to ensure that every block that was performed was captured in the database. Intraoperative and postoperative complications were tracked until their resolution. Blocks were categorized by type and as single-injection or catheter (continuous) blocks.A total of 14,917 regional blocks, performed on 13,725 patients, were accrued from April 1, 2007 through March 31, 2010. There were no deaths or complications with sequelae lasting >3 months (95% CI 0-2:10,000). Single-injection blocks had fewer adverse events than continuous blocks, although the most frequent events (33% of all events) in the latter group were catheter-related problems. Ninety-five percent of blocks were placed while patients were under general anesthesia. Single-injection caudal blocks were the most frequently performed (40%), but peripheral nerve blocks were also frequently used (35%), possibly driven by the widespread use of ultrasound (83% of upper extremity and 69% of lower extremity blocks).Regional anesthesia in children as commonly performed in the United States has a very low rate of complications, comparable to that seen in the large multicenter European studies. Ultrasound may be increasing the use of peripheral nerve blocks. Multicenter collaborative networks such as the Pediatric Regional Anesthesia Network can facilitate the collection of detailed prospective data for research and quality improvement.

Abstract

While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase γ deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam™ (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, **p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, *p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population.

Abstract

The safety and utility of pediatric epidural analgesia is well established, but the risk of permanent neurological injury is unknown and largely must be extrapolated from adult literature. In this article we present a series of 4 cases of longterm or permanent neurologic complications associated with epidural analgesia. Possible mechanisms of injury and implications for practice are discussed.

Abstract

Analgesic trials pose unique scientific, ethical, and practical challenges in pediatrics. Participants in a scientific workshop sponsored by the US Food and Drug Administration developed consensus on aspects of pediatric analgesic clinical trial design. The standard parallel-placebo analgesic trial design commonly used for adults has ethical and practical difficulties in pediatrics, due to the likelihood of subjects experiencing pain for extended periods of time. Immediate-rescue designs using opioid-sparing, rather than pain scores, as a primary outcome measure have been successfully used in pediatric analgesic efficacy trials. These designs maintain some of the scientific benefits of blinding, with some ethical and practical advantages over traditional designs. Preferred outcome measures were recommended for each age group. Acute pain trials are feasible for children undergoing surgery. Pharmacodynamic responses to opioids, local anesthetics, acetaminophen, and nonsteroidal antiinflammatory drugs appear substantially mature by age 2 years. There is currently no clear evidence for analgesic efficacy of acetaminophen or nonsteroidal antiinflammatory drugs in neonates or infants younger than 3 months of age. Small sample designs, including cross-over trials and N of 1 trials, for particular pediatric chronic pain conditions and for studies of pain and irritability in pediatric palliative care should be considered. Pediatric analgesic trials can be improved by using innovative study designs and outcome measures specific for children. Multicenter consortia will help to facilitate adequately powered pediatric analgesic trials.

Abstract

Neuropathic pain is relatively uncommon in children. Although some syndromes closely resemble those found in adults, the incidence and course of the condition can vary substantially in children, depending on developmental status and contextual factors. There are some neuropathic pain syndromes that are rare and relatively unique to the pediatric population. This article discusses the array of neuropathic pain conditions in children and available treatment strategies. Data are limited by small numbers and few randomized controlled trials. Research and clinical implications are discussed.

Abstract

The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel alpha(2)-delta ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.

Abstract

Difficulty assessing pain has been cited as one of the primary reasons for infrequent and inadequate assessment and analgesia for children with cognitive impairment (CI). Several behavioral observational pain tools have been shown to have good psychometric properties for pain assessment in this population; however, routine clinical use may depend largely on their pragmatic qualities. We designed this study to evaluate pragmatic attributes or clinical utility properties of three recently developed pain assessment tools for children with CI.A sample of clinicians from three medical centers were asked to review 15 videotaped observations of children with CI, recorded during their first three postoperative days during participation in a previous study. Participants scored pain using the revised-Face, Legs, Activity, Cry, Consolability (r-FLACC) tool (individualized for the child during the previous study) for five observations, the noncommunicative Non-Communicating Children's Pain Checklist-Postoperative Version (NCCPC-PV) for five, and the Nursing Assessment of Pain Intensity (NAPI) for five observations. After their review of all segments, participants completed the Clinical Utility Attributes Questionnaire (CUAQ) ranking three attributes of clinical utility; complexity, compatibility, and relative advantage.Five physicians and 15 nurses comprised the sample. There was excellent agreement between the coded pain scores (i.e., mild, moderate, severe pain) assigned using all tools and r-FLACC scores assigned by original observers (88%-98% exact agreement; kappa 0.71-0.96). The internal consistency or reliability of the CUAQ was supported by high alpha values for each of the subscales (alpha = 0.84-0.93). Subscale and total CUAQ scores were higher for the r-FLACC and NAPI compared with the NCCPC-PV. The r-FLACC had similar scores for complexity, but slightly higher scores for compatibility, relative advantage, and total utility compared with the NAPI.We found that clinicians rated the complexity, compatibility, relative advantage, and overall clinical utility higher for the r-FLACC and NAPI compared with the NCCPC-PV, suggesting that these tools may be more readily adopted into clinical practice.

Abstract

Significant progress in understanding the physiology, clinical correlates, and consequences of neonatal pain have resulted in greater attention to pain management during neonatal intensive care. A number of nonpharmacological therapies have been investigated, including nonnutritive sucking, with and without sucrose use, swaddling or facilitated tucking, kangaroo care, music therapy, and multi-sensorial stimulation. Although the efficacy of these approaches is clearly evident, they cannot provide analgesia for moderate or severe pain in the neonate. Further, some of these therapies cannot be effectively applied to all populations of critically ill neonates. Acupuncture, an ancient practice in Chinese medicine, has gained increasing popularity for symptom control among adults and older children. Acupuncture may provide an effective nonpharmacological approach for the treatment of pain in neonates, even moderate or severe pain, and should be considered for inclusion in a graduated multidisciplinary algorithm for neonatal pain management.

Abstract

As video-assisted thoracoscopic surgery has become more common in paediatric patients, the use of single lung ventilation in children has also increased. Single lung ventilation in young children is performed by either advancing a tracheal tube into the mainstem bronchus opposite the side of surgery or by positioning a bronchial blocker into the mainstem bronchus on the operative side. Techniques for placing a variety of bronchial blockers outside the tracheal tube have been described. We describe a technique for placement of a new bronchial blocker through an indwelling tracheal tube using a multiport adaptor and a fibreoptic bronchoscope.

Abstract

Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study's research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after.The use of ultra-short-acting opioids may be an appropriate technique for infants less than 2 mo old when tracheal extubation after surgery is anticipated.

Abstract

Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.Abnormal breathing patterns can follow anesthesia in infants after surgical repair of pyloric stenosis. Occasionally, these patterns can be associated with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

Abstract

We conducted this retrospective study to document the efficacy and safety, and demonstrate the spectrum of indications for subcutaneously tunneled epidural catheters in the management of prolonged pain in pediatric patients. The charts of 25 patients with prolonged pain that was unresponsive to conventional opioid therapy (10: end stage malignancy, 8: extensive abdominal surgery, 7: trauma, etc.) and who received thoracic, lumbar, or caudal tunneled epidural catheters between 1995 and 1999 were reviewed for efficacy and catheter-related complications (infection or bleeding at the insertion site, toxicity related to local anesthetics, tachyphylaxis and respiratory depression). Tunneled epidural catheters were effective in providing extended analgesia in all subjects. In 14 patients with chronic pain, cumulative 48-h enteral and parenteral opioid requirements were reduced or eliminated after catheter insertion. Catheters remained in place for a median of 11 days (range, 4--240 days) until there was no further need for parenteral analgesia (n = 15), death because of the underlying disease (n = 6), accidental removal (n = 2), or possible infection (n = 2). No serious local or systemic complications (meningitis, epidural abscess, systemic infection, epidural hematoma, or spinal cord injury; seizures, local anesthetic toxicity) occurred related to this technique. Five patients were discharged from the hospital with the catheter for home analgesic therapy. The use of a percutaneously inserted, subcutaneously tunneled epidural catheter is safe, effective, and provides pain relief in situations in which conventional analgesic therapy either fails or is impractical. The technique is one that may be of great value to children suffering from pain.Children and adolescents with pain may safely have a spinal catheter placed for a period of time without undo risk of infection or other complications. Spinal catheters provide excellent pain relief, often eliminating the need for riskier medications for painful events such as wound cleansing and dressing changes.

Abstract

The past decade has brought about an explosion of knowledge about the physiology of nociception and many new techniques for pain relief, new analgesic drugs, and new applications of old analgesic drugs. These techniques include methods of opioid administration by transdermal and transmucosal absorption and the use of neuraxial analgesia for the management of pain in children. Interest in the use of regional anesthesia in children has been rekindled, and analgesic properties and pre-emptive analgesic properties of many agents not typically considered analgesics, such as clonidine and ketamine, have been recognized. Perhaps the greatest advance has been the paradigm shift in the recognition that pain not only exists in infants and children but also is a significant cause of morbidity and even mortality. Given the unprecedented interest in pain management in adults and children, physicians can now look forward to the development of new methods of drug delivery and of receptor-specific drugs that divorce analgesia from the untoward side effects of existing analgesics. Improvement in the quality of life of hospitalized children also will occur.

Abstract

Regional anesthesia during general anesthesia has become increasingly popular in recent years. Most pediatric anesthesiologists are proponents of this practice, and believe that surgical morbidity is reduced, but controversy remains regarding safety. Neuraxial anesthesia during general anesthesia is especially controversial. Unfortunately, outcome studies are lacking but the literature reflects an absence of reported serious morbidity or mortality.

Abstract

Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who were less than 51 wk postconceptional age were assigned to either the general anesthesia group (GA: atropine, halothane, and nitrous oxide) or the spinal anesthesia group (SA: hyperbaric tetracaine). Twelve-hour, three-channel continuous recordings of respiratory rate (chest wall impedance), electrocardiogram (ECG), and hemoglobin O2 saturation (SpO2) were obtained preoperatively and after surgery. These were analyzed for short (11-15s) and long (> 15 s) apnea spells, periodic breathing, and episodes of hemoglobin oxygen desaturation and bradycardia. Infants in the GA group had lower postoperative minimum SpO2 (68.7% +/- 11.4%) and minimum heart rate (79 bpm +/- 19) than infants in the SA group (80.7% +/- 9.2%, and 109 bpm +/- 30, respectively; P < 0.05) and had lower postoperative minimum SpO2 and minimum heart rate than they had preoperatively (79.0% +/- 13.7%, and 93 bpm +/- 31, respectively; P < 0.05); pre- and postoperative studies in the SA group did not differ. There were no differences in the incidence of postoperative central apnea. We conclude that spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and bradycardia in formerly premature infants undergoing inguinal herniorrhaphy.

Abstract

Phantom sensations and pain occur with an unknown frequency in children. We hypothesized that such experiences are common among children, and occur more often than is recognized by health-care personnel. Children and adolescents, ages 5-19 years, who had undergone limb amputation in the past 10 years, served as subjects for this retrospective study. Subjects were divided into three major groups depending upon the indication for amputation: congenital deformity (CD), trauma/infection (TI), and cancer (Ca). Surveys assessing phantom sensations and phantom pain were mailed to children and their parents/guardians. The incidence of phantom sensations was 100% in each group, and phantom pain occurred in the overwhelming majority. Both types of phantom phenomena began within days of surgery for almost all patients. Seventy-five percent of children and adolescents who had experienced phantom pain also had preoperative limb pain. At the time of the study, phantom pain had resolved in only 35% of the subjects. Phantom pain was documented in the medical records of only 40% of those answering positively to questions regarding phantom pain on the questionnaire. We conclude that phantom pain occurs commonly in children and adolescents. The association of preoperative pain in the diseased extremity and the later occurrence of phantom pain suggests that preoperative regional anesthesia may prevent phantom pain.

Abstract

The authors compared the duration of analgesia and the frequency of side effects of three doses of caudal epidural morphine in children aged 1.2-7.9 yr. Caudal catheters were inserted in 32 children, randomly assigned to receive 0.033 mg.kg-1, 0.067 mg.kg-1, or 0.10 mg.kg-1 of preservative-free morphine for analgesia after major surgical procedures below the diaphragm. The first dose of caudal morphine was mixed with 0.25 ml.kg-1 of 1% lidocaine to confirm correct caudal catheter placement. By assessment of periodic pain scores and the time intervals between administration of caudal morphine and the recurrence of pain, the authors found that the mean (+/- SD) duration of analgesia was significantly longer after 0.10 mg.kg-1 (13.3 +/- 4.7 h) than after either 0.033 mg.kg-1 or 0.067 mg.kg-1 (10.0 +/- 3.3 and 10.4 +/- 4.2 h, respectively) (P less than 0.02). The frequency of vomiting, pruritus, and urinary retention was similar in each group. Vomiting was less common in patients who had nasogastric drainage than in patients who were fed soon after surgery (P less than 0.05). Delayed respiratory depression occurred in one child after 0.10 mg.kg-1 of caudal morphine. Caudal morphine, 0.033-0.10 mg.kg-1, provided prolonged analgesia in children. The authors recommend 0.033 mg.kg-1 of caudal morphine as an initial dose for children.

Abstract

Diabetic ketoacidosis (DKA) is the most common cause of death of juvenile-onset diabetics, and as such represents an important issue for pediatricians. In this article, the author reviews the endocrinology of insulin and the glucose counter-regulatory hormones, which are the basis for the development of DKA. The effects of hyperglycemia and acidosis upon organ physiology are detailed, and this serves as the foundation for subsequent discussion of the management of the patient with DKA. Finally, the author summarizes current strategies for prevention of DKA in patients with diabetes.

Abstract

We compared the efficacy, duration, and side effects of preservative-free morphine injected into the caudal space in children, with caudal bupivacaine and with intravenous morphine administration for relief of postoperative pain. Forty-six children, ages 1-16 yr, were randomly assigned to receive intravenous morphine (control group), caudal bupivacaine (0.25%, 1 ml/kg), or caudal morphine (0.5 mg/ml, 0.1 mg/kg). In half the patients given caudal morphine, the morphine was mixed with a dose of lidocaine adequate to produce sacral analgesia, to confirm correct caudal injection of the morphine. Caudal injections were performed at the end of surgery. Time until the first required postoperative intravenous morphine dose was recorded for each patient. The duration of analgesia was significantly greater with caudal morphine (median 12 hr, P less than 0.02) than with caudal bupivacaine (median 5 hr), and both were greater than with intravenous morphine in control patients (median 45 min). Urinary retention, pruritus, and nausea appeared with slightly greater frequency in the caudal morphine group, but no delayed respiratory depression occurred. Caudal morphine (0.5 mg/ml, 0.1 mg/kg) provided 8-24 hr of analgesia in children without a significantly greater incidence of side effects than caudal bupivacaine or intravenous morphine.

Abstract

Clinically apparent cerebral edema is a rare and often fatal complication of diabetic ketoacidosis. To determine whether subclinical brain swelling occurs more commonly, we obtained cranial CT scans in six children with diabetic ketoacidosis treated with fluid resuscitation and continuous low-dose insulin therapy. Control scans were obtained before hospital discharge. Compared with the scans during convalescence, the early scans of all six children showed a narrowing of the brain's ventricular system, compatible with brain swelling. Average changes in diameter were 1.3 +/- 0.1 mm for the third ventricle and 3.7 +/- 0.8 mm for the lateral ventricles (P less than 0.01). In addition, a narrowing of the subarachnoid spaces was subjectively noted during a blind reading of the early scans. Although no single scan was overtly indicative of cerebral edema, the data suggest that subclinical brain swelling may be a common occurrence during treatment of diabetic ketoacidosis in children. Sequential CT scans of the brain may provide a means of evaluating modifications of standard therapy aimed at preventing cerebral edema.

Abstract

Postdural puncture headache (PDPH) is an uncommon sequel of lumbar puncture in children. When conservative treatment with bed rest, hydration, and caffeine are ineffective, epidural blood patches are recommended and are generally effective. The purpose of this report was to highlight that when lumbar epidural blood patches fail to eliminate PDPH, diagnostic evaluation should be performed and alternative treatment sought.An unusual case is described of an 11-year-old boy with PDPH, which was successfully managed with a ventral (anterior) epidural blood patch and epidural saline infusion after headache and other symptoms failed to resolve after conservative treatment and conventionally performed blood patches.Ineffectiveness of conservative measures and epidural blood patches performed posteriorly to resolve PDPH should lead the physician both to question the diagnosis of PDPH by pursuing radiographic confirmation of a cerebral spinal fluid leak and, furthermore, identification of its location to best direct further therapy.

Abstract

Some topics in the clinical management of regional anesthesia in children remain controversial. To evaluate and come to a consensus regarding some of these topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a joint committee practice advisory on pediatric regional anesthesia (PRA).Representatives from both ASRA and ESRA comprised the joint committee practice advisory on PRA. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Experts selected controversial topics in PRA.The performance of PRA under general anesthesia or deep sedation is associated with acceptable safety and should be viewed as the standard of care (Evidence B2 and Evidence B3). Because of the difficulty interpreting a negative test dose, the use of test dosing should remain discretionary (Evidence B4). The use of either air-loss of resistance or saline-loss of resistance techniques is supported by expert opinion, but the literature supporting one technique over the other is sparse and controversial; when used appropriately, each technique may be safely used in children. There are no current evidence-based data that the use of RA increases the risk for acute compartment syndrome or delays its diagnosis in children.High-level evidence is not yet available for the topics evaluated, and most recommendations are based on Evidence B studies. The ESRA/ASRA recommendations intend to provide guidance for the safe practice of regional anesthesia in children.

Abstract

We describe an instance in which complete paraplegia was evident immediately postoperatively after apparently uneventful lumbar epidural-general anesthesia in a patient with Morquio Type A syndrome (Morquio A) with moderate thoracic spinal stenosis.A 16-yr-old male with Morquio A received lumbar epidural-general anesthesia for bilateral distal femoral osteotomies. Preoperative imaging had revealed a stable cervical spine and moderate thoracic spinal stenosis with a mild degree of spinal cord compression. Systolic blood pressure (BP) was maintained within 20% of the pre-anesthetic baseline value. The patient sustained a severe thoracic spinal cord infarction. The epidural anesthetic contributed to considerable delay in the recognition of the diagnosis of paraplegia.This experience leads us to suggest that, in patients with Morquio A, it may be prudent to avoid the use of epidural anesthesia without very firm indication, to support BP at or near baseline levels in the presence of even moderate spinal stenosis, and to avoid flexion or extension of the spinal column in intraoperative positioning. If the spinal cord/column status is unknown or if the patient is known to have any degree of spinal stenosis, we suggest that the same rigorous BP support practices that are typically applied in other patients with severe spinal stenosis, especially stenosis with myelomalacia, should apply to patients with Morquio A and that spinal cord neurophysiological monitoring should be employed. In the event that cord imaging is not available, e.g., emergency procedures, it would be prudent to assume the presence of spinal stenosis.

Abstract

A practice advisory on regional anesthesia in children in 2008, published in this journal, supported the placement of regional blocks in children under general anesthesia (GA). Interscalene brachial plexus (IS) blocks were specifically excluded, based on case reports (level 3 evidence) of injury, which occurred predominantly in heavily sedated or anesthetized adult patients. Apart from case reports, there is a paucity of data that explore the safety of IS blocks placed in patients under GA, and the level of evidence available on which to base recommendations is limited.Querying the database of the Pediatric Regional Anesthesia Network (PRAN), we report on the incidence of postoperative neurological symptoms, local anesthetic systemic toxicity, and other reported adverse events in children receiving IS blocks under GA or sedated.A total of 518 interscalene blocks were performed, 390 under GA and 123 with the patient sedated or awake (5 cases had missing status); 472 of these were single injection, and 46 involved the placement of infusion catheters. Eighty-eight percent of blocks were placed with ultrasound guidance, 7.7% with no location device, and 2.5% with a nerve stimulator. No local anesthetic systemic toxicity, postoperative neurological symptoms, cardiovascular complications, or dural puncture was reported in this cohort. There were 1 vascular puncture and 1 postoperative infection. These negative results are compatible with 0 to 7.7/1000 events for each of these complications for IS blocks placed under GA. There was no paralysis, motor block, or sensory deficit beyond the expected block duration time.Analyzing interscalene blocks in children placed under GA, we identified no serious adverse events. The upper limit of the confidence interval for these events is similar to that in awake or sedated adults receiving IS blocks. Based on these prospectively collected data, placement of IS blocks under GA in children is no less safe than placement in awake adults, calling into question the American Society of Regional Anesthesia and Pain Medicine advisory proscribing GA during IS block in pediatric patients.

Abstract

Current approaches to classification of chronic pain conditions suffer from the absence of a systematically implemented and evidence-based taxonomy. Moreover, existing diagnostic approaches typically fail to incorporate available knowledge regarding the biopsychosocial mechanisms contributing to pain conditions. To address these gaps, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration and the American Pain Society (APS) have joined together to develop an evidence-based chronic pain classification system called the ACTTION-APS Pain Taxonomy. This paper describes the outcome of an ACTTION-APS consensus meeting, at which experts agreed on a structure for this new taxonomy of chronic pain conditions. Several major issues around which discussion revolved are presented and summarized, and the structure of the taxonomy is presented. ACTTION-APS Pain Taxonomy will include the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. In coming months, expert working groups will apply this taxonomy to clusters of chronic pain conditions, thereby developing a set of diagnostic criteria that have been consistently and systematically implemented across nearly all common chronic pain conditions. It is anticipated that the availability of this evidence-based and mechanistic approach to pain classification will be of substantial benefit to chronic pain research and treatment.The ACTTION-APS Pain Taxonomy is an evidence-based chronic pain classification system designed to classify chronic pain along the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors.

Abstract

There has been an increasing tendency for anesthesiologists to be responsible for providing sedation or anesthesia during chest CT imaging in young children. Anesthesia-related atelectasis noted on chest CT imaging has proven to be a common and troublesome problem, affecting image quality and diagnostic sensitivity.To evaluate the safety and effectiveness of a standardized anesthesia, lung recruitment, controlled-ventilation technique developed at our institution to prevent atelectasis for chest CT imaging in young children.Fifty-six chest CT scans were obtained in 42 children using a research-based intubation, lung recruitment and controlled-ventilation CT scanning protocol. These studies were compared with 70 non-protocolized chest CT scans under anesthesia taken from 18 of the same children, who were tested at different times, without the specific lung recruitment and controlled-ventilation technique. Two radiology readers scored all inspiratory chest CT scans for overall CT quality and atelectasis. Detailed cardiorespiratory parameters were evaluated at baseline, and during recruitment and inspiratory imaging on 21 controlled-ventilation cases and 8 control cases.Significant differences were noted between groups for both quality and atelectasis scores with optimal scoring demonstrated in the controlled-ventilation cases where 70% were rated very good to excellent quality scans compared with only 24% of non-protocol cases. There was no or minimal atelectasis in 48% of the controlled ventilation cases compared to 51% of non-protocol cases with segmental, multisegmental or lobar atelectasis present. No significant difference in cardiorespiratory parameters was found between controlled ventilation and other chest CT cases and no procedure-related adverse events occurred.Controlled-ventilation infant CT scanning under general anesthesia, utilizing intubation and recruitment maneuvers followed by chest CT scans, appears to be a safe and effective method to obtain reliable and reproducible high-quality, motion-free chest CT images in children.

Abstract

Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults.To determine factors important for success in renal transplantation in children.Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry.One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery.Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.

Abstract

To report a case of respiratory depression after a small dose of caudal morphine administered to a 15-mo-old child.A 15 mo, 9.8 kg boy underwent ureteral reimplantation with general endotracheal anaesthesia and 10 ml bupivacaine 0.25% (2.5 mg.kg-1). Ninety minutes after the bupivacaine, 0.4 mg (1 mg.ml-1, 0.4 ml, 0.04 mg.kg-1) preservative-free morphine was injected after negative aspiration. Slightly more than two hours after caudal morphine, the patient became lethargic and developed decreases in oxygen saturation (to 62%) without change in heart rate or respiratory rate. Intravenous naloxone 0.1 mg (0.01 mg.kg-1) markedly improved his level of consciousness. Racemic epinephrine was administered for treatment of coincident stridor. The patient required 11 hr continuous naloxone infusion (0.001-0.002 mg.kg-1.hr-1) in the intensive care unit. He was discharged on the second postopertive day without further complication.Respiratory depression can occur in children greater than one year of age, even when small doses of caudal morphine are used. Decreased arterial oxygen saturation and lethargy are important heralds. A normal respiratory rate despite substantial hypoxaemia argues that pulse oximetry (without supplemental oxygen where possible) has a clear advantage over impedance pneumography for electronic monitoring.

Abstract

Tracheal obstruction of the newborn caused by cervical masses such as teratomas and cystic hygromas can result in a profound hypoxic insult and even death, owing to an inability to establish an adequate airway after birth. Prenatal sonographic diagnosis of these congenital anomalies permits (1) anticipation of an airway problem at the time of delivery and (2) formulation of an algorithm for airway management while oxygen delivery to the baby is maintained through the placental circulation. This is the report of a fetus in whom a large anterior cervical cystic hygroma was detected by prenatal ultrasonography. A multidisciplinary management team was assembled, and an algorithm for airway management was developed. Elective cesarean delivery of the fetal head and thorax, under conditions of uterine tocolysis, permitted a controlled evaluation of the airway and endotracheal intubation while oxygen supply to the infant was maintained through the placenta. The baby remained intubated, and 2 days later underwent subtotal excision of the cervical cystic hygroma. Pharmacological maintenance of the feto-placental circulation after hysterotomy is an invaluable adjunct to airway management of the neonate with prenatally diagnosed tracheal obstruction.

Abstract

Influenza B virus causes epidemic infection in normal children, but only one case of infection in an immunocompromised solid organ transplant (SOT) recipient has been reported. Characterization of the clinical course of influenza B virus infection in pediatric SOT recipients may increase the utilization of preventive and therapeutic interventions by pediatricians caring for these immunocompromised children.Retrospective chart review of patients whose respiratory viral cultures yielded influenza B from January 1989 through March 1992.Twelve pediatric SOT recipients with influenza B virus infection were identified. These included five renal, four hepatic, and three cardiac allograft recipients, ranging from 19 months to 17 years 9 months of age (median 6 years 2 months). The posttransplant interval ranged from 6 weeks to 4 years 6 months (average 26.7 months). No patient had been immunized against influenza. Exposure histories were documented for eight children; five of these occurred in the hospital.Clinical symptoms included fever (12/12), respiratory (11/12), or gastrointestinal complaints (8/12). Five patients had neurologic involvement; one died of uncal herniation. Ten children were hospitalized (median duration, 3 days; range, 2 to 79 days). Two patients (post-transplant interval, 3 to 8 months) required mechanical ventilation, and one of these received aerosolized ribavirin. Three children had concurrent allograft rejection.Influenza B infection is potentially life-threatening in pediatric SOT recipients. We recommend annual immunization of pediatric SOT recipients, their household contacts, and health care workers. Prospective studies are needed to evaluate the efficacy of influenza vaccination in pediatric SOT recipients.

Abstract

Postoperative pain management in children is a topic that has been neglected in the past but is currently an active field of interest and effort. Clearly, the child's cognitive understanding of and emotional response to pain are different than an adult's, and these differences make pain assessment and control more difficult. Ongoing work to develop more accurate techniques of estimating pain intensity in children may have helpful results. The effects of untreated pain in children are similar to those in adults but may have more long-term consequences in children. In the past, postoperative pain treatment in children was often inadequate, but newer techniques, such as continuous infusion of opioids, patient-controlled analgesia, epidural administration of opioids, and regional analgesia, hold promise for improved care in the future.

Abstract

The effect of halothane on Ca2+ uptake or release by the sarcoplasmic reticulum (SR) was compared in the newborn and adult rabbit myocardium. The sarcolemma of right ventricular myocardium was disrupted (skinned) by homogenization. Fiber bundles were dissected from the homogenate, mounted on tension transducers, and immersed sequentially in five solutions that loaded Ca2+ into the SR, then in solutions containing either 2 or 25 mM caffeine to release SR-stored Ca2+, resulting in transient tension development. Experimental solutions were saturated with halothane in N2 gas during Ca2+ uptake by SR, Ca2+ release by SR, or during both SR Ca2+ uptake and release. Halothane (0.5-1.7%) resulted in dose-dependent depression of SR Ca2+ uptake in both newborn and adult skinned fibers. Less tension transient depression resulted in newborn (35%) than adult skinned fibers (49.5%, P less than 0.05) with 0.5% halothane exposure during SR Ca2+ uptake. Similar depression resulted in newborn (53.7% and 73.4%) and adult fibers (65.2% and 77.9%) with 1.0% and 1.7% halothane. Halothane had little effect on SR Ca2+ release by 25 mM caffeine but enhanced submaximal SR Ca2+ release by 2 mM caffeine more in newborn than adult myocardium. Increased Ca2+ efflux from newborn SR may contribute to the greater sensitivity of intact newborn cardiac muscle to exposure to halothane.

Abstract

The effect of halothane on maximal and submaximal Ca2+-activated tension development of the contractile proteins of newborn and adult cardiac muscle from rabbits was determined. Right ventricular muscle was removed from newborn and adult rabbits, and the sarcolemma was disrupted (skinned) by homogenization. Fiber bundles were dissected from the homogenate and mounted on tension transducers. Fiber bundles were alternately immersed in relaxing solution [( Ca2+] less than 10(-9) M) and contracting solutions (various [Ca2+] from 10(-5.6) to 10(-3.8) M), which were saturated with 100% N2 alone or with three concentrations of halothane-N2 mixture. In the absence of halothane, newborn skinned myocardial fibers were slightly more sensitive to submaximal Ca2+ concentrations than were adult myocardial fibers. [Ca2+] required for 50% maximum tension were 10(-5.43) M and 10(-5.31) M, respectively (P less than 0.05). Halothane (1-3%) decreased the maximal Ca2+-activated tension (at [Ca2+] = 10(-3.8) M) similarly in adult and newborn myocardial fibers in a dose-dependent fashion. Tension was reduced by 5.9% for each 1% increase in halothane concentration. Halothane also decreased the sensitivity of adult myocardial skinned fibers to submaximal Ca2+ concentrations (10(-5.6) M to 10(-5.0) M) by shifting the Ca2+-tension response curve to the right. Only 3% halothane decreased the sensitivity of newborn myocardial skinned fibers to Ca2+. The authors conclude that halothane causes less depression of Ca2+ activation of the contractile proteins in newborn than adult rabbit myocardium and that this effect of halothane cannot account for greater negative inotropy of halothane in the newborn.

Abstract

The Scientific Board of the California Medical Association presents the following inventory of items of progress in anesthesiology. Each item, in the judgement of a panel of knowledge physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers, or scholars to stay abreast of these items of progress in anesthesiology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Anesthesiology of the California Medical Association and the summaries were prepared under its direction.

Abstract

The effect of halothane on myocardial contractility was studied in isolated right ventricular muscle preparations from newborn and adult rabbits. Right ventricular strips were mounted in oxygenated Krebs' solution and stimulated with supramaximal voltages at 1.0 Hz, while isometric force of contraction was continuously recorded. Halothane (0.4, 0.7, and 1.1%) caused a significant dose-dependent depression of both peak developed tension (42, 61, and 70%, respectively) and maximum rate of rise of isometric tension (40, 56, and 64%, respectively) of newborn myocardium. Newborn myocardial preparations exhibited approximately 20% greater depression of contractility than adult myocardium at each concentration studied (P less than 0.05), thus a parallel shift of the dose-response curves was observed. It was concluded that halothane exerts a potent depressant effect on newborn myocardium that is greater than that on adult myocardium. The depression effect of halothane on the newborn myocardium may contribute to its hypotensive effect in newborn infants.

Abstract

Plasma thyroxine (T4) and reverse triiodothyronine (rT3) concentrations have been measured in chronically catheterised sheep fetuses during the last third of gestation. In some animals T4 and rT3 concentrations fell before delivery but there was no change in the t4/rT3 ratio. In several serially sampled fetuses a small rise in plasma triiodothyronine concentration has been demonstrated in the days preceding delivery. Infusion of cortisol to fetuses commencing at 130 days of gestation (term 147 days) with the simultaneous administration of progesterone to delay labour resulted in changes in T4 and rT3 concentrations which were similar to those normally seen at term. The nature of the changes in the peripheral metabolism of T4 around the time of birth are discussed.

Abstract

A method of continuous monitoring of fetal intravascular PO2 at various sites in the circulation in the chronically catheterized fetal sheep for up to 41 days (mean 11.1 days) has been compared with values obtained in blood samples measured extracorporeally in a standard blood gas analyzer. A double-blind comparison of the two methods showed that there was no bias between the two methods and correlation was 0.94. The stability of the electrodes was superior to that of a conventional blood gas analyzer. In every animal there was continuous variability of fetal vascular PO2. In the period from 105 to 126 days' gestation we noted the presence of slow increases in basal uterine tone that we have called "contractures". The frequency of these contractures was very regular at approximately one per hour. The frequency of these contracutres was very regular at approximately one per hour. There is a statistically significant related fall in fetal vascular PO2 in relation to these contractures. Well-coordinated uterine contractions during labor also produced a fall in fetal vascular PO2 that was related to the uterine activity.

Abstract

A detailed description is given of a method to section the pituitary stalk of the fetal lamb after 105 days gestational age. The approach to the stalk is made through a window in the frontal bone. In order to prevent regeneration of the hypothalamo-pituitary connections a silicone plate is introduced through the probe used to fracture the stalk. The surgical outcome and viability of 11 pituitary stalk sectioned fetuses is described over periods of up to 23 days. The presence of pituitary infarction following stalk section was related to damage of the anterior hypophysial vesssels if the probe was deviated from the mid-line at any time in its course. The effect of this procedure on fetal plasma T4 and PRL concentrations and the initiation of premature labour by the continuous infusion of cortisol into the fetus is described.

Abstract

Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uni-nucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be supppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism.

Abstract

The effect of cortisol infusion on plasma T4 and T3 concentrations has been investigated in the fetal lamb at 130-134 days of gestation. Infusion of cortisol at rates equivalent to one-third the quantity produced by the fetus at the time of parturition results in a significant fall in fetal plasma T4 concentration and a significant rise in fetal plasma T3 concentration. Delay in the initiation of labor as a result of progesterone administration to the ewe did not prevent the changes in the fetal thyroid axis. These modifications of thyroid function therefore appear to be caused by the infusion of cortisol rather than to be secondary to the induction of labor.